Preliminary experiments indicate that the chronotropic response to isoproterenol by the embryonic chick heart can be blocked by prior incubation of the tissue with phospholipase-C. The inotropic response is little affected and inherent rate and contractility are not significantly altered. Noninnervated (4-day-old) embryonic chick hearts and isolated rat heart cells in culture will be treated with various concentrations of enzymes (phosphatidases, trypsin, subtilisin) for varying periods of time and their subsequent sensitivity to the cardiostimulant effects of isoproterenol determined. If receptor inactivation can be realized attempts will be made to prevent this by classical receptor protection methods (incubation with enzyme in presence of isoproterenol). Efforts to reactivate unresponsive receptors by incubation or culture with appropriate substrates will be made.